Broadly neutralizing antibodies recognizing different antigenic epitopes act synergistically against the influenza B virus.

The discovery of broadly neutralizing monoclonal antibodies against influenza viruses has raised hope for the successful development of new antiviral drugs. However, due to the speed and variety of mutations in influenza viruses, single-component antibodies that recognize specific epitopes are susceptible to viral escape and have limited efficacy when administration is delayed. Hence, it is necessary to develop alternative strategies with better antiviral activity. Influenza B virus infection can cause severe illness in children and the elderly. Commonly used anti-influenza drugs have low clinical efficacy against influenza B virus. In this study, we investigated the antiviral efficacy of combinations of representative monoclonal antibodies targeting different antigenic epitopes against the influenza B virus. We found that combinations of antibodies recognizing the hemagglutinin (HA) head and stem regions showed a stronger neutralizing activity than single antibodies and other antibody combinations in vitro. In addition, we found that pair-wise combinations of antibodies recognizing the HA head region, HA stem region, and neuraminidase enzyme-activated region showed superior antiviral activity than single antibodies in both mouse and ferret in vivo protection assays. Notably, these antibody combinations still displayed good antiviral efficacy when treatment was delayed. Mechanistic studies further revealed that combining antibodies recognizing different epitope regions resulted in extremely strong antibody-dependent cell-mediated cytotoxicity, which may partly explain their superior antiviral effects. Together, the findings of this study provide new avenues for the development of better antiviral drugs and vaccines against influenza viruses.

Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirus.

The worldwide outbreak of the monkeypox virus (MPXV) has become a "Public Health Emergency of International Concern" (PHEIC). Severe monkeypox virus infection can be fatal, however, effective therapeutic methods are yet to be developed. Mice were immunized with A35R protein and A29L protein of MPXV, and the binding and neutralizing activities of the immune sera against poxvirus-associated antigens and viruses were identified. A29L protein and A35R protein-specific monoclonal antibodies (mAbs) were generated and their antiviral activities of these mAbs were characterized in vitro and in vivo. Immunization with the MPXV A29L protein and A35R protein induced neutralizing antibodies against the orthopoxvirus in mice. None of the mAbs screened in this study against A35R could effectively neutralize the vaccinia virus (VACV), while three mAbs against A29L protein, 9F8, 3A1 and 2D1 were confirmed to have strong broad binding and neutralizing activities against orthopoxvirus, among which 9F8 showed the best neutralizing activity. 9F8, 3A1, and 2D1 recognized different epitopes on MPXV A29L protein, showing synergistic antiviral activity in vitro against the VACV Tian Tan and WR strains; the best activity was observed when the three antibodies were combined. In the vivo antiviral prophylactic and therapeutic experiments, 9F8 showed complete protective activity, whereas 3A1 and 2D1 showed partial protective activity. Similarly, the three antibodies showed synergistic antiviral protective activity against the two VACVs. In conclusion, three mAbs recognized different epitopes on MPXV A29L protein were developed and showed synergistic effects against orthopoxvirus.

Cannabis Seed Oil Alleviates Experimental Atherosclerosis by Ameliorating Vascular Inflammation in Apolipoprotein-E-Deficient Mice.

In recent decades, epidemiological, clinical, and experimental studies have demonstrated that a diet with antioxidant or anti-inflammatory function plays a central role in the prevention of atherosclerosis (AS). The purpose of this study was to explore the effects of Cannabis seed oil (CO) administration on in vitro antioxidant capacity as well as blood lipid profiles, lipid peroxidation, inflammatory response, and endothelial cell integrity. Female ApoE-/- mice were fed a high-cholesterol diet and administrated with CO or phosphate-buffered saline (PBS) and seal oil by gavage for 8 weeks. The results show that CO administration reduced the levels of serum triglycerides and low-density lipoprotein cholesterol at week 6. Additionally, a decrease in serum tumor necrosis factor α and nitric oxide was also observed. Moreover, results from CD31 staining and scanning electron microscopy revealed that CO treatment alleviated the endothelial cell damage and lipid deposition induced by a high-cholesterol diet. The ratio of lesion area to the total aorta area was 19.57% for the CO group, which was lower than the PBS control group (24.67%). Collectively, CO exerted anti-atherosclerotic effects by modulating serum lipid profiles and inflammatory responses and improving endothelial cell integrity and arterial lipid deposition. The results provide a promising preventive strategy for the early progression of AS.

Programmable Color in a Free-Standing Photonic Microgel Film with Ultra-Fast Response.

In this work, a free-standing microgel film with programmable and angle-independent structural color is prepared via a simple but effective method. Dried poly(styrene-N-isopropylacrylamide-acrylic acid) (pStNIPAAmAA) microgels were stabilized by inter-microgel crosslinking, and thus, only microgels were used to build the optical hydrogel. The free-standing microgel film displayed tunable structural color by the swelling/deswelling of the microgels under external stimuli, such as temperature, pH, ionic strength, and organic solvent. Moreover, the structural color of the film is angle-independent for the disordered microgel arrays. It is worth noting that programmable color stripes which have the panther chameleon's ability to change skin color are successfully fabricated by patterning microgels with different thermoresponsivities. More importantly, the microgel film has an ultrafast response to temperature (1.41 s from 20 to 40 °C) and pH (2.24 s from pH 8.3 to pH 2.0), much faster than that of most optical materials reported in previous studies.

Cell Adhesion and Migration Behaviors on Patterned Thermoresponsive Microgel Stripes.

Cell adhesion and migration behaviors are influenced by their surrounding environments. In this work, patterned poly(N-isopropylacrylamide-styrene) (pNIPAAmSt) microgel stripes, which can provide a more complex environment, were fabricated on polyethyleneimine (PEI)-precoated glass substrate, and their effects on cell adhesion and migration behavior were investigated. The results showed that patterned cell layers can be formed on the space regions either by selective adhesion of the cells or by detaching the attached cells from the thermoresponsive microgel stripes via mild temperature stimuli. The migration behavior of the cells was affected by both the cell types and the width of the microgel stripes. The wider the microgel stripe, the harder it is for the cells to migrate, and the longer the patterned cell layers can be conserved. It is worth noting that the cell-cell interaction in the cocultured system plays a key role in the cell migration process. This work may offer a platform to study the adhesion and migration behavior of mono/cocultured cells in a more controllable system.